Halo-substituted 1,4-dihydro-4-oxo-quinoline-3-carboxylic acid derivatives and their corresponding naphthyridines (hereinafter quinolones) are known to be effective antibacterial agents for human and animal use (see, for example, U.S. Pat. No. 4,730,000). Typical starting materials used in the synthesis of such quinolones include halo-substituted benzoic acids and their corresponding esters and acetophenones. It has been found, however, that known methods of preparing these compounds suffer from a number of drawbacks, including the need for expensive or hard-to-obtain reagents; materials hazards such as those associated with the use and decomposition of diazonium salts; and reactions having commercially undesirable selectives and/or yields.
In particular, 2-chloro-4,5-difluorobenzoic acid (CDFBA), 2,4,5-trifluorobenzoic acid (TFBA) and their respective analogous acetophenones are advantageous starting materials for quinolone synthesis. Preparations of these compounds have been described in U.S. Pat. No. 4,833,270, issued May 28, 1989, and in the German Laid-Open Patent Application DE 38 40 371, published May 31, 1990. There remains, however, a need for a process offering an improved means of obtaining these and related quinolone precursors.